Gene interactions and pathways from curated databases and text-mining
J Biol Chem 1994, PMID: 8144662

Shc is the predominant signaling molecule coupling insulin receptors to activation of guanine nucleotide releasing factor and p21ras-GTP formation.

Sasaoka, T; Draznin, B; Leitner, J W; Langlois, W J; Olefsky, J M

Insulin stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and She in Rat1 fibroblasts overexpressing wild type insulin receptors. We investigated the relative role of IRS-1 and She in insulin activation of guanine nucleotide releasing factor (GNRF) and p21ras-GTP formation. The time course of insulin-stimulated tyrosine phosphorylation of IRS-1 was rapid, whereas Shc phosphorylation was relatively slow. Growth factor receptor bound protein-2 (Grb2) associated with IRS-1 rapidly and gradually dissociated after 5 min, whereas Grb2 association with Shc was slower and reached a maximum at 10 min after insulin stimulation. Thus, the kinetics of Grb2 association with IRS-1 and She corresponded closely to the time course of tyrosine phosphorylation of IRS-1 and Shc, respectively. Importantly, 3-13-fold more Grb2 was associated with Shc than with IRS-1. In addition, the kinetics of insulin-stimulated GNRF activity and p21ras-GTP formation corresponded more closely to the time course of Shc phosphorylation than to the kinetics of IRS-1 phosphorylation. Furthermore, immunoprecipitation of Shc proteins from cell lysates of insulin-stimulated cells removed 67% of the GNRF activity, whereas precipitation of IRS-1 had a negligible effect on GNRF activity. Thus, although both IRS-1 and Shc associate with Grb2, the current results indicate that Shc plays a more important role than IRS-1 in insulin stimulation of GNRF activity and subsequent p21ras-GTP formation.

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Text Mining Data

p21ras-GTP ⊣ IRS-1: " We investigated the relative role of IRS-1 and She in insulin activation of guanine nucleotide releasing factor ( GNRF ) and p21ras-GTP formation "

insulin ⊣ IRS-1: " We investigated the relative role of IRS-1 and She in insulin activation of guanine nucleotide releasing factor ( GNRF ) and p21ras-GTP formation "

insulin → p21ras-GTP: " We investigated the relative role of IRS-1 and She in insulin activation of guanine nucleotide releasing factor ( GNRF ) and p21ras-GTP formation "

IRS-1 → insulin: " The time course of insulin stimulated tyrosine phosphorylation of IRS-1 was rapid, whereas Shc phosphorylation was relatively slow "

p21ras-GTP → insulin: " In addition, the kinetics of insulin stimulated GNRF activity and p21ras-GTP formation corresponded more closely to the time course of Shc phosphorylation than to the kinetics of IRS-1 phosphorylation "

insulin — Shc: " Thus, although both IRS-1 and Shc associate with Grb2, the current results indicate that Shc plays a more important role than IRS-1 in insulin stimulation of GNRF activity and subsequent p21ras-GTP formation "

Manually curated Databases

  • NCI Pathway Database Insulin Pathway: Insulin Receptor/Insulin/SHC/GRB2/Sos1 complex (INSR-INS-SHC1-GRB2-SOS1) → HRAS/GTP complex (HRAS) (modification, activates)
    Evidence: assay
  • NCI Pathway Database Insulin Pathway: Insulin Receptor/Insulin/SHC/GRB2/Sos1 complex (INSR-INS-SHC1-GRB2-SOS1) → HRAS/GDP complex (HRAS) (modification, activates)
    Evidence: assay
  • NCI Pathway Database Insulin Pathway: HRAS/GTP complex (HRAS) → HRAS/GDP complex (HRAS) (modification, collaborate)
    Evidence: assay
  • NCI Pathway Database Insulin Pathway: Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos complex (INSR-INS-SHC1-SOS1-GRB2-IRS1) → HRAS/GTP complex (HRAS) (modification, activates)
    Evidence: assay
  • NCI Pathway Database Insulin Pathway: Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos complex (INSR-INS-SHC1-SOS1-GRB2-IRS1) → SHC/SHIP complex (SHC1-INPP5D) (modification, activates)
    Evidence: assay
  • NCI Pathway Database Insulin Pathway: Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos complex (INSR-INS-SHC1-SOS1-GRB2-IRS1) → HRAS/GDP complex (HRAS) (modification, activates)
    Evidence: assay
  • NCI Pathway Database Insulin Pathway: HRAS/GTP complex (HRAS) → HRAS/GDP complex (HRAS) (modification, collaborate)
    Evidence: assay
  • NCI Pathway Database Insulin Pathway: SHC/SHIP complex (SHC1-INPP5D) → HRAS/GDP complex (HRAS) (modification, inhibits)
    Evidence: assay
In total, 30 gene pairs are associated to this article in curated databases